Temporal changes in the risk of six-month post-covid symptoms: a national population-based cohort study.

It is unclear how the risk of post-covid symptoms evolved during the pandemic, especially before the spread of Severe Acute Respiratory Syndrome Coronavirus 2 variants and the availability of vaccines. We used modified Poisson regressions to compare the risk of six-month post-covid symptoms and their associated risk factors according to the period of first acute covid: during the French first (March-May 2020) or second (September-November 2020) wave. Non-response weights and multiple imputation were used to handle missing data. Among participants aged 15 or more in a national population-based cohort, the risk of post-covid symptoms was 14.6% (95% CI: 13.9%, 15.3%) in March-May 2020, versus 7.0% (95% CI: 6.3%, 7.7%) in September-November 2020 (adjusted RR: 1.36, 95% CI: 1.20, 1.55). For both periods, the risk was higher in the presence of baseline physical condition(s), and it increased with the number of acute symptoms. During the first wave, the risk was also higher for women, in the presence of baseline mental condition(s), and it varied with educational level. In France in 2020, the risk of six-month post-covid symptoms was higher during the first than the second wave. This difference was observed before the spread of variants and the availability of vaccines.

CT venography for the diagnosis of postpartum venous thromboembolism: a prospective multi-center cohort study.

OBJECTIVES: To assess the role of CT venography (CTV) in the diagnosis of venous thromboembolism (VTE) during the postpartum period. MATERIALS AND METHODS: This multicenter prospective cohort study was conducted between April 2016 and April 2020 in 14 university hospitals. All women referred for CT pulmonary angiography (CTPA) for suspected pulmonary embolism (PE) within the first 6 weeks postpartum were eligible. All CTPAs were performed on multidetector CT machines with the usual parameters and followed by CTV of the abdomen, pelvis, and proximal lower limbs. On-site reports were compared to expert consensus reading, and the added value of CTV was assessed for both. RESULTS: The final study population consisted of 123 women. On-site CTPA reports mentioned PE in seven women (7/123, 5.7%), all confirmed following expert consensus reading, three involving proximal pulmonary arteries and four limited to distal arteries. Positive CTV was reported on-site in nine women, five of whom had negative and two indeterminate CTPAs, bringing the VTE detection rate to 11.4% (14/123) (95%CI: 6.4-18.4, p = 0.03). Expert consensus reading confirmed all positive on-site CTV results, but detected a periuterine vein thrombosis in an additional woman who had a negative CTPA, increasing the VTE detection rate to 12.2% (15/123) (95%CI: 7.0-19.3, p = 0.008). Follow-up at 3 months revealed no adverse events in this woman, who was left untreated. Median Dose-Length-Product was 117 mGy.cm for CTPA and 675 mGy.cm for CTPA + CTV. CONCLUSION: Performing CTV in women suspected of postpartum PE doubles the detection of venous thromboembolism, at the cost of increased radiation exposure. CLINICAL RELEVANCE STATEMENT: CTV can help in the decision-making process concerning curative anticoagulation in women with suspected postpartum PE, particularly those whose CTPA results are indeterminate or whose PE is limited to the subsegmental level. KEY POINTS: Postpartum women are at risk of pulmonary embolism, and CT pulmonary angiography can give equivocal results. CT venography (CTV) positivity increased the venous thromboembolism detection rate from 5.7 to 11.4%. CTV may help clinical decision-making, especially in women with indeterminate CTPA results or subsegmental emboli.

Metrological performances of the global chronic morbidity indicator of the Minimum European Health Module and implications for chronic disease prevalence and socioeconomic gradient estimations.

BACKGROUND: Although the global chronic morbidity indicator (GCMI) of the Minimum European Health Module (MEHM) was not specifically designed to monitor chronic disease in the population, it is increasingly used for this purpose in Europe and elsewhere. However, its metrological characteristics have seldom been examined, with various sensitivity issues being raised. The present study investigated the metrological performances of the GCMI and analyzed its implications in terms of prevalence and demographic and socioeconomic gradients of chronic conditions in the population. METHODS: We used data from two large French nationwide representative surveys with cross-sectional and longitudinal data conducted between 2010 and 2021. The surveys used MEHM and collected data on numerous chronic conditions and socioeconomic indicators. Criterion and predictive validity of the GCMI regarding chronic conditions and the resultant socioeconomic gradients were compared with indicators based on reports of individual chronic conditions. RESULTS: GCMI sensitivity to capture chronic conditions varied from <20 to 80% depending on the chronic condition. Number of chronic conditions, gender, age and education were also associated with GCMI endorsement. However, the GCMI was predictive of mortality and activity limitations independently of individual conditions. CONCLUSION: The varying lack of sensitivity depending on the chronic condition and the respondent's sociodemographic status may bias estimates of demographic and socioeconomic gradients compared with indicators based on reports of individual chronic conditions. Differences between GCMI and list-based approaches should be more cautiously considered when monitoring chronic conditions in the population. These approaches should be viewed as complementary rather than contradictory or interchangeable.

Multimorbidity and frailty are associated with poorer SARS-CoV-2-related outcomes: systematic review of population-based studies.

BACKGROUND: Estimating the risks and impacts of COVID-19 for different health groups at the population level is essential for orienting public health measures. Adopting a population-based approach, we conducted a systematic review to explore: (1) the etiological role of multimorbidity and frailty in developing SARS-CoV-2 infection and COVID-19-related short-term outcomes; and (2) the prognostic role of multimorbidity and frailty in developing short- and long-term outcomes. This review presents the state of the evidence in the early years of the pandemic. It was conducted within the European Union Horizon 2020 program (No: 101018317); Prospero registration: CRD42021249444. METHODS: PubMed, Embase, World Health Organisation COVID-19 Global literature on coronavirus disease, and PsycINFO were searched between January 2020 and 7 April 2021 for multimorbidity and 1 February 2022 for frailty. Quantitative peer-reviewed studies published in English with population-representative samples and validated multimorbidity and frailty tools were considered. RESULTS: Overall, 9,701 records were screened by title/abstract and 267 with full text. Finally, 14 studies were retained for multimorbidity (etiological role, n = 2; prognostic, n = 13) and 5 for frailty (etiological role, n = 2; prognostic, n = 4). Only short-term outcomes, mainly mortality, were identified. An elevated likelihood of poorer outcomes was associated with an increasing number of diseases, a higher Charlson Comorbidity Index, different disease combinations, and an increasing frailty level. DISCUSSION: Future studies, which include the effects of recent virus variants, repeated exposure and vaccination, will be useful for comparing the possible evolution of the associations observed in the earlier waves.

Collider and reporting biases involved in the analyses of cause of death associations in death certificates: an illustration with cancer and suicide.

BACKGROUND: Mortality data obtained from death certificates have been studied to explore causal associations between diseases. However, these analyses are subject to collider and reporting biases (selection and information biases, respectively). We aimed to assess to what extent associations of causes of death estimated from individual mortality data can be extrapolated as associations of disease states in the general population. METHODS: We used a multistate model to generate populations of individuals and simulate their health states up to death from national health statistics and artificially replicate collider bias. Associations between health states can then be estimated from such simulated deaths by logistic regression and the magnitude of collider bias assessed. Reporting bias can be approximated by comparing the estimates obtained from the observed death certificates (subject to collider and reporting biases) with those obtained from the simulated deaths (subject to collider bias only). As an illustrative example, we estimated the association between cancer and suicide in French death certificates and found that cancer was negatively associated with suicide. Collider bias, due to conditioning inclusion in the study population on death, increasingly downwarded the associations with cancer site lethality. Reporting bias was much stronger than collider bias and depended on the cancer site, but not prognosis. RESULTS: The magnitude of the biases ranged from 1.7 to 9.3 for collider bias, and from 4.7 to 64 for reporting bias. CONCLUSIONS: These results argue for an assessment of the magnitude of both collider and reporting biases before performing analyses of cause of death associations exclusively from mortality data. If these biases cannot be corrected, results from these analyses should not be extrapolated to the general population.

Insulin allergy: a diagnostic and therapeutic strategy based on a retrospective cohort and a case-control study.

AIMS/HYPOTHESIS: Insulin allergy is a rare but significant clinical challenge. We aimed to develop a management workflow by (1) validating clinical criteria to guide diagnosis, based on a retrospective cohort, and (2) assessing the diagnostic performance of confirmatory tests, based on a case-control study. METHODS: In the retrospective cohort, patients with suspected insulin allergy were classified into three likelihood categories according to the presence of all (likely insulin allergy; 26/52, 50%), some (possible insulin allergy; 9/52, 17%) or none (unlikely insulin allergy; 17/52, 33%) of four clinical criteria: (1) recurrent local or systemic immediate or delayed hypersensitivity reactions; (2) reactions elicited by each injection; (3) reactions centred on the injection sites; and (4) reactions observed by the investigator (i.e. in response to an insulin challenge test). All underwent intradermal reaction (IDR) tests. A subsequent case-control study assessed the diagnostic performance of IDR, skin prick and serum anti-insulin IgE tests in ten clinically diagnosed insulin allergy patients, 24 insulin-treated non-allergic patients and 21 insulin-naive patients. RESULTS: In the retrospective cohort, an IDR test validated the clinical diagnosis in 24/26 (92%), 3/9 (33%) and 0/14 (0%) likely, possible and unlikely insulin allergy patients, respectively. In the case-control study, an IDR test was 80% sensitive and 100% specific and identified the index insulin(s). The skin prick and IgE tests had a marginal diagnostic value. Patients with IDR-confirmed insulin allergy were treated using a stepwise strategy. CONCLUSIONS/INTERPRETATION: Subject to validation, clinical likelihood criteria can effectively guide diabetologists towards an insulin allergy diagnosis before undertaking allergology tests. An IDR test shows the best diagnostic performance. A progressive management strategy can subsequently be implemented. Continuous subcutaneous insulin infusion is ultimately required in most patients. CLINICALTRIALS: gov: NCT01407640.

Risk of intracranial meningioma with three potent progestogens: A population-based case-control study.

BACKGROUND AND PURPOSE: A dose-dependent association between the use of cyproterone acetate (CPA) and intracranial meningioma has been identified but data for other potent progestogens are scarce. The association was assessed between intracranial meningioma surgery and exposure to three potent progestogens: CPA (≥25 mg/day), nomegestrol acetate (NOMAC) (3.75-5 mg/day) and chlormadinone acetate (CMA) (2-10 mg/day). METHODS: In this nationwide population-based case-control study, cases underwent surgery for intracranial meningioma in France from 2009 to 2018. They were matched to five control subjects for sex, year of birth and area of residence. Progestogen exposure was defined as progestogen use within the year before surgery for cases or the same date for their controls. RESULTS: In total, 25,216 cases were included (75% women, median age 58 years). Progestogen exposure was noted for 9.9% of cases (2497/25,216) and 1.9% (2382/126,080) of controls, with an odds ratio (OR) of 6.7 (95% confidence interval [CI] 6.3-7.1). The OR was 1.2 (1.0-1.4) for short-term use (<1 year) and 9.5 (8.8-10.2) for prolonged use. A strong association was identified for prolonged use of CPA (OR = 22.7, 95% CI 19.5-26.4), NOMAC (OR = 6.5, 95% CI 5.8-7.2) and CMA (OR = 4.7, 95% CI 4.5-5.3). Progestogen exposure increased the risk of meningioma for all histological grades and anatomical sites, particularly for the anterior and middle skull base: OR = 35.7 (95% CI 26.5-48.2) and 23.9 (95% CI 17.8-32.2) for CPA. The estimated number of attributable cases was 2124 (95% CI 2028-2220) (212/year). CONCLUSION: A strong association between prolonged exposure to potent progestogens and surgery for meningioma was observed. The risk increased from CMA to NOMAC to CPA. Individuals should be informed of this risk.

Estimating and characterizing the burden of multimorbidity in the community: A comprehensive multistep analysis of two large nationwide representative surveys in France.

BACKGROUND: Given the increasing burden of chronic conditions, multimorbidity is now a priority for healthcare and public health systems worldwide. Appropriate methodological approaches for assessing the phenomenon have not yet been established, resulting in inconsistent and incomplete descriptions. We aimed to estimate and characterize the burden of multimorbidity in the adult population in France in terms of number and type of conditions, type of underlying mechanisms, and analysis of the joint effects for identifying combinations with the most deleterious interaction effects on health status. METHODS AND FINDINGS: We used a multistep approach to analyze cross-sectional and longitudinal data from 2 large nationwide representative surveys: 2010/2014 waves of the Health, Health Care, and Insurance Survey (ESPS 2010-2014) and Disability Healthcare Household Survey 2008 (HSM 2008), that collected similar data on 61 chronic or recurrent conditions. Adults aged ≥25 years in either ESPS 2010 (14,875) or HSM 2008 (23,348) were considered (participation rates were 65% and 62%, respectively). Longitudinal analyses included 7,438 participants of ESPS 2010 with follow-up for mortality (97%) of whom 3,798 were reinterviewed in 2014 (52%). Mortality, activity limitation, self-reported health, difficulties in activities/instrumental activities of daily living, and Medical Outcomes Study Short-Form 12-Item Health Survey were the health status measures. Multiple regression models were used to estimate the impact of chronic or recurrent conditions and multimorbid associations (dyads, triads, and tetrads) on health status. Etiological pathways explaining associations were investigated, and joint effects and interactions between conditions on health status measures were evaluated using both additive and multiplicative scales. Forty-eight chronic or recurrent conditions had an independent impact on mortality, activity limitations, or perceived heath. Multimorbidity prevalence varied between 30% (1-year time frame) and 39% (lifetime frame), and more markedly according to sex (higher in women), age (with greatest increases in middle-aged), and socioeconomic status (higher in less educated and low-income individuals and manual workers). We identified various multimorbid combinations, mostly involving vasculometabolic and musculoskeletal conditions and mental disorders, which could be explained by direct causation, shared or associated risk factors, or less frequently, confounding or chance. Combinations with the highest health impacts included diseases with complications but also associations of conditions affecting systems involved in locomotion and sensorial functions (impact on activity limitations), and associations including mental disorders (impact on perceived health). The interaction effects of the associated conditions varied on a continuum from subadditive and additive (associations involving cardiometabolic conditions, low back pain, osteoporosis, injury sequelae, depression, and anxiety) to multiplicative and supermultiplicative (associations involving obesity, chronic obstructive pulmonary disease, migraine, and certain osteoarticular pathologies). Study limitations included self-reported information on chronic conditions and the insufficient power of some analyses. CONCLUSIONS: Multimorbidity assessments should move beyond simply counting conditions and take into account the variable impacts on health status, etiological pathways, and joint effects of associated conditions. In particular, the multimorbid combinations with substantial health impacts or shared risk factors deserve closer attention. Our findings also suggest that multimorbidity assessment and management may be beneficial already in midlife and probably earlier in disadvantaged groups.

Choice of Systemic Drugs for the Management of Moderate-to-severe Psoriasis: A Cross-country Comparison Based on National Health Insurance Data.

Current management of moderate-to-severe psoriasis may be heterogeneous between European countries, probably due to differences in the organization of care. The aim of this study was to compare the utilization of systemic treatments for psoriasis between 2 coun-tries. All adults with psoriasis who were registered in the French (SNDS) and the Dutch (VEKTIS) national health insurance databases between 2012 and 2016 were eligible for inclusion. In France, 105,035 (15%) of 684,156 patients and, in the Netherlands, 37,405 (28.6%) of 130,822 patients received at least a systemic agent. In France, the proportion of patients treated with systemic agents was constant, while the type of drugs dispensed shifted from non-biological to biological agents. In the Netherlands, the first systemic treatment was methotrexate and, in France, acitretin. In France, the choice of the first biologic was much more variable than it was in the Netherlands, where a large proportion of patients were dispensed ustekinumab. This study highlights discrepancies between France and the Netherlands concerning the choice of first non-biologic agent and first biologic agent for patients with psoriasis. These discrepancies may be due to differences in the healthcare systems between the 2 countries.

Alteration in perceived health status of those aged 55 to 65 between 2010 and 2017 in France: role of socioeconomic determinants.

BACKGROUND: While life expectancy increases, it is necessary to evaluate whether the additional years are lived in good health, particularly in order to adapt the health care provision and social measures available to support these individuals. Since the 1990s, improvements in perceived health and capacities have been observed among older people, however the changes appear to be far less favourable among the working-age population and, in particular, the generation of people approaching retirement age. The aim of this study was to examine the change in the perceived health status of those aged 55 to 65 in France and investigate the role of socioeconomic factors in this change. METHODS: Self-reported health (SRH), chronic condition and activity limitation were assessed in 2010 and in 2017 in the French Health Barometer, a general population phone survey conducted on over 25,000 persons living in the community. The prevalence of all three indicators in 2017, and their evolution between 2010 and 2017 were studied according to the main socioeconomic determinants. RESULTS: Between 2010 and 2017, there was a sharp increase in the proportion of individuals aged 55-65 reporting poor SRH, chronic condition or activity limitation. A much more marked deterioration was observed in the three indicators among those aged 55-65 than in older age groups, as well as different changes according to socioeconomic determinants. The category of workers with an average level of education was particularly affected by the deterioration. CONCLUSIONS: This study confirms that the generation approaching retirement age presents a more significant deterioration in health status than those of previous generations. The question of how these trends will be reflected in terms of the burden of dependency at later ages remains open and should encourage increased monitoring of and prevention among this population in future years.

Incidence of and Risk Factors for Systemic Adverse Events After Screening or Primary Diagnostic Colonoscopy: A Nationwide Cohort Study.

OBJECTIVES: To estimate the systemic serious adverse event (SAE) rates after colonoscopy and to identify their risk factors. METHODS: A nationwide cohort study was conducted using the comprehensive French claims databases SNDS (National Health Data System). Patients aged 30 years and over who underwent a first screening or diagnostic colonoscopy in 2010-2015 were included. The rates of cardiovascular and renal SAEs were estimated within 5 days after colonoscopy. The standardized incidence ratios were calculated to compare these incidence rates with those of the same events in the general population, and the associated risk factors were assessed by multilevel logistic regression. RESULTS: Among the 4,088,799 included patients (median age, 59 years [interquartile range = 50-67]; 55.2% women; 30.1% with a Charlson index score ≤1), the 5-day SAE incidence rate was 2.8/10,000 procedures for shock, 0.87/10,000 for myocardial infarction, 1.9/10,000 for stroke, 2.9/10,000 for pulmonary embolism, 5.5/10,000 for acute renal failure, and 3.3/10,000 for urolithiasis. These SAEs occurred 3.3 to 15.8 times more often during the first 5 days after colonoscopy than expected in the general population. Thirty-day mortality rates ranged from 2.2/1,000 cases of urolithiasis to 268.1/1,000 cases of shock. Increasing age was associated with an increasing incidence of SAEs. Risks of shock and acute renal failure were associated with a greater number of comorbidities than the other SAEs. Colonoscopies in university hospitals were associated with higher risks, reflecting patient selection processes. DISCUSSION: The systemic SAEs can be associated with a substantial mortality. They should be taken into account when deciding colonoscopy, in addition to perforation and bleeding, particularly in elderly patients with multiple comorbidities.

Trajectory analysis combining pain and physical function in individuals with knee and hip osteoarthritis: results from the French KHOALA cohort.

OBJECTIVES: The aims of this study were to identify homogeneous subgroups of knee and/or hip OA patients with distinct trajectories of the combination of pain and physical function (PF) over time and to determine the baseline factors associated with these trajectories. METHODS: We used data from the Knee and Hip Osteoarthritis Long-term Assessment (KHOALA) cohort, a French population-based cohort of 878 patients with symptomatic knee and/or hip OA. Pain and PF were measured annually over 5 years with the Medical Outcomes Study Short Form 36 questionnaire. First, trajectory models were estimated with varying numbers of groups for each of the outcomes separately then fitted into a multi-trajectory model. We used multinomial logistic regression to determine the baseline characteristics associated with each trajectory. RESULTS: Univariate four-class models were identified as most appropriate for pain and PF. Comparison of separate trajectories showed that 41% of patients included in the severe functional limitations trajectory did not belong to the more severe pain trajectory (Cramér's V statistic = 0.45). Group-based multi-trajectory modelling revealed four distinct trajectories of pain and PF. On multivariate analyses, female sex, older age, high Kellgren grade, low physical activity intensity, low psychosocial distress score (high distress) and low vitality score were associated with the more severe symptoms trajectory. CONCLUSION: Over 5 years, we identified four distinct trajectories combining pain and PF. Management of weight, fatigue and psychosocial distress and the practice of physical activity seem important to maintain function and limit pain in patients with lower-limb OA.

Effectiveness and Safety of Reference Infliximab and Biosimilar in Crohn Disease: A French Equivalence Study.

Background: CT-P13 is a biosimilar of the reference product (RP) infliximab, with demonstrated efficacy and safety for some inflammatory arthritides. It was approved for the treatment of Crohn disease (CD) on that basis, without specific studies examining its effects in CD. Objective: To compare the effectiveness and safety of CT-P13 and RP in infliximab-naive patients with CD. Design: Comparative equivalence cohort study. Setting: Système National des Données de Santé (SNDS), a French nationwide health administrative database (1 March 2015 to 30 June 2017). Patients: 5050 infliximab-naive patients with CD who were older than 15 years, had started treatment with RP (n = 2551) or CT-P13 (n = 2499), and had no other indications for infliximab. Measurements: The primary outcome was a composite end point of death, CD-related surgery, all-cause hospitalization, and reimbursement of another biologic therapy. Equivalence was defined as a 95% CI of the hazard ratio (HR) of CT-P13 versus RP in a multivariable marginal Cox model situated within prespecified margins (0.80 to 1.25). Results: Overall, 1147 patients in the RP group and 952 patients in the CT-P13 group met the composite end point (including 838 and 719 hospitalizations, respectively). In multivariable analysis of the primary outcome, CT-P13 was equivalent to RP (HR, 0.92 [95% CI, 0.85 to 0.99]). No differences in safety outcomes were observed between the 2 groups: serious infections (HR, 0.82 [CI, 0.61 to 1.11]), tuberculosis (HR, 1.10 [CI, 0.36 to 3.34]), and solid or hematologic cancer (HR, 0.66 [CI, 0.33 to 1.32]). Limitation: The SNDS does not contain all relevant clinical data (for example, disease activity). Conclusion: This analysis of real-world data indicates that the effectiveness of CT-P13 is equivalent to that of RP for infliximab-naive patients with CD. No difference was observed for safety outcomes. Primary Funding Source: Caisse Nationale de l'Assurance Maladie.

Cardiovascular effect of discontinuing statins for primary prevention at the age of 75 years: a nationwide population-based cohort study in France.

AIMS: The role of statin therapy in primary prevention of cardiovascular disease in persons older than 75 years remains a subject of debate with little evidence to support or exclude the benefit of this treatment. We assessed the effect of statin discontinuation on cardiovascular outcomes in previously adherent 75-year-olds treated for primary prevention. METHODS AND RESULTS: A population-based cohort study using French national healthcare databases was performed, studying all subjects who turned 75 in 2012-14, with no history of cardiovascular disease and with a statin medication possession ratio ≥80% in each of the previous 2 years. Statin discontinuation was defined as three consecutive months without exposure. The outcome was hospital admission for cardiovascular event. The hazard ratio comparing statin discontinuation with continuation was estimated using a marginal structural model adjusting for both baseline and time-varying covariates (cardiovascular drug use, comorbidities, and frailty indicators). A total of 120 173 subjects were followed for an average of 2.4 years, of whom 17 204 (14.3%) discontinued statins and 5396 (4.5%) were admitted for a cardiovascular event. The adjusted hazard ratios for statin discontinuation were 1.33 [95% confidence interval (CI) 1.18-1.50] (any cardiovascular event), 1.46 (95% CI 1.21-1.75) (coronary event), 1.26 (95% CI 1.05-1.51) (cerebrovascular event), and 1.02 (95% CI 0.74-1.40) (other vascular event). CONCLUSION: Statin discontinuation was associated with a 33% increased risk of admission for cardiovascular event in 75-year-old primary prevention patients. Future studies, including randomized studies, are needed to confirm these findings and support updating and clarification of guidelines on the use of statins for primary prevention in the elderly.

Burden of fractures in France: incidence and severity by age, gender, and site in 2016.

PURPOSE: Fractures are common events, but the exact incidence and severity of fractures have not been clearly determined for most anatomical sites. We estimated the incidence and severity of fractures in France regardless of the anatomical site. METHODS: Observational cross-sectional study in France in 2016 based on the national health data system. All incident fractures in patients 20 years and older were included. We determined the anatomical fracture site (12 sites) and the severity using a 4-point scale (outpatient care, hospitalization, surgery, and in-hospital death). RESULTS: We identified 562,094 incident fractures, predominantly occurring in women (319,858: 56.9%); with a mean age of 63.6 years, and an exponential increase after the age of 70 years. Distal upper limb (172,591: 30.7%), distal lower limb (84,602: 15.1%), and femoral neck (78,766: 14.0%) accounted for more than one-half of all fractures. Sex and age of onset distributions varied widely according to fracture sites, with earlier onset for distal lower limb fractures (mean age: 54.2 years) and distal upper limb fractures (mean age: 55.2 years) with a men predominance for skull fractures. Only 105,165 (18.7%) fractures were treated on an outpatient basis; 11,913 (2.1%) in-hospital deaths occurred in patients with a mean age of 79.5 years. High mortality was observed for skull (12.9%), rib (4.9%), and femoral fractures (femoral neck 4.3% and proximal lower limb 4.2%). CONCLUSION: We estimated the incidence of fractures in France by sex and anatomical site. We also showed that fractures remain common and serious life events, especially in older people.

Patient, Procedure, and Endoscopist Risk Factors for Perforation, Bleeding, and Splenic Injury After Colonoscopies.

BACKGROUND & AIMS: We investigated perforations, bleeding, and splenic injuries after screening or diagnostic colonoscopies to identify patient-, procedure-, endoscopist-, and facility-associated risk factors. METHODS: We analyzed data from the SNIIRAM-PMSI national claims databases in France. A total of 4,088,799 patients, 30 years or older, undergoing a first screening or diagnostic colonoscopy from 2010 through 2015 were identified. Rates of severe adverse events (SAEs) were estimated using stringent and broad definitions. Risk factors associated with perforations and major bleeding were estimated using multilevel logistic regression models, adjusted for patient, colonoscopy, and endoscopist characteristics. RESULTS: Perforation rates ranged from 3.5 (stringent definition) to 7.3 (broad definition) per 10,000 procedures, bleeding rates ranged from 6.5 to 23.1 per 10,000 procedures, and splenic injury rates ranged from 0.20 to 0.34 per 10,000 procedures. Rates of 30-day mortality were 13.2 per 1000 bleeds, 29.2 per 1000 perforations, and 36.1 per 1000 splenic injuries (stringent definitions). Patient characteristics associated with SAEs were increasing age (especially for perforation), cancer, and cardiovascular comorbidities. Procedure characteristics associated with SAEs included polypectomy-especially of polyps larger than 1 cm with an increased risk of perforation (odds ratio, 4.1; 95% CI, 3.4-5.0) and bleeding (odds ratio, 13.3; 95% CI, 11.7-15.1). Less-experienced endoscopists and endoscopists who performed a smaller number of colonoscopies were independently associated with a risk of SAEs. CONCLUSION: In an analysis of national claims databases in France, we found SAEs related to screening and diagnostic colonoscopies to be more frequent in older patients, in patients with comorbidities, and with less-experienced endoscopists. Patients at risk of SAE should be identified and colonoscopies should be performed or supervised by experienced endoscopists.

Statins for primary prevention of cardiovascular disease and the risk of acute kidney injury.

PURPOSE: To investigate the risk of acute kidney injury (AKI) in subjects initiating statin therapy for primary prevention of cardiovascular disease (CVD). METHODS: A nationwide cohort study using French hospital discharge and claims databases was performed, studying subjects from the general population aged 40 to 75 years in 2009, with no history of CVD and no lipid-lowering drugs during the preceding 3-year period, followed for up to 7 years. Exposure to statins (type, dose, and time since first use) and to other drugs for CVD risk was assessed. The primary outcome was hospital admission for AKI. RESULTS: The cohort included 8 236 279 subjects, 818 432 of whom initiated a statin for primary prevention. During 598 487 785 person-months exposed to statins, 700 events were observed, corresponding to an incidence of AKI of 4.59 per 10 000 person-years (7.01 in men, 3.01 in women). AKI mainly occurred in the context of organ failure, sepsis, and genitourinary disease. A 19% increased rate of AKI (hazard ratio = 1.19, 95%CI: 1.08-1.31) was observed in men exposed to statins, whereas no increase in the overall risk of AKI was observed in women. However, exposure to high-potency statins was associated with a 72% to 116% increased risk in both genders and a dose-effect relationship observed for rosuvastatin and atorvastatin. No temporal pattern of occurrence nor interaction with drugs for CVD risk was observed. CONCLUSIONS: Although the overall risk of AKI appears moderately increased, more attention should be paid to renal function in subjects taking statins for primary prevention both in clinical practice and from a research viewpoint.

Qualitative Methods Used to Generate Questionnaire Items: A Systematic Review.

A systematic review of articles using qualitative methods to generate questionnaire items identified in MEDLINE and PsycINFO from 2000 to 2014 was carried out. Articles were analyzed for (a) year of publication and journal domain, (b) qualitative data collection methods, (c) method of data content analysis, (d) professional experts' input in item generation, and (e) debriefing of the newly developed items. In total, 371 articles were included and results showed (a) an acceleration of published articles, (b) individual interviews and focus groups were common ways of generating items and no emergent approach was identified, (c) the content analysis was usually not described (43% of articles), (d) experts were involved in eliciting concepts in less than a third of articles, (e) 61% of articles involved a step of further submission of newly developed items to the population of interest. This review showed an insufficient reporting of qualitative methods used to generate new questionnaires despite previous recommendations.

An automated computed tomography score for the cystic fibrosis lung.

OBJECTIVES: To develop an automated density-based computed tomography (CT) score evaluating high-attenuating lung structural abnormalities in patients with cystic fibrosis (CF). METHODS: Seventy adult CF patients were evaluated. The development cohort comprised 17 patients treated with ivacaftor, with 45 pre-therapeutic and follow-up chest CT scans. Another cohort of 53 patients not treated with ivacaftor was used for validation. CT-density scores were calculated using fixed and adapted thresholds based on histogram characteristics, such as the mode and standard deviation. Visual CF-CT score was also calculated. Correlations between the CT scores and forced expiratory volume in 1 s (FEV1% pred), and between their changes over time were assessed. RESULTS: On cross-sectional evaluation, the correlation coefficients between FEV1%pred and the automated scores were slightly lower to that of the visual score in the development and validation cohorts (R = up to -0.68 and -0.61, versus R = -0.72 and R = -0.64, respectively). Conversely, the correlation to FEV1%pred tended to be higher for automated scores (R = up to -0.61) than for visual score (R = -0.49) on longitudinal follow-up. Automated scores based on Mode + 3 SD and Mode +300 HU showed the highest cross-sectional (R = -0.59 to -0.68) and longitudinal (R = -0.51 to -0.61) correlation coefficients to FEV1%pred. CONCLUSIONS: The developed CT-density score reliably quantifies high-attenuating lung structural abnormalities in CF. KEY POINTS: • Automated CT score shows moderate to good cross-sectional correlations with FEV 1 %pred . • CT score has potential to be integrated into the standard reporting workflow.

Risk of hospitalisation and death related to baclofen for alcohol use disorders: Comparison with nalmefene, acamprosate, and naltrexone in a cohort study of 165 334 patients between 2009 and 2015 in France.

PURPOSE: Baclofen is widely used off-label for alcohol use disorders (AUD) in France, despite its uncertain efficacy and safety, particularly at high doses. This study was designed to evaluate the safety of this off-label use compared to the main approved drugs for AUD (acamprosate, naltrexone, nalmefene). METHODS: This cohort study from the French Health Insurance claims database included patients, aged 18 to 70 years, with no serious comorbidity (assessed by the Charlson score) initiating baclofen or approved drugs for AUD between 2009 and 2015. The risk of hospitalisation or death associated with baclofen, at variable doses over time (from low doses <30 mg/day to high doses ≥180 mg/day), compared to approved drugs, was evaluated by a Cox model adjusted to sociodemographic and medical characteristics. RESULTS: The cohort included 165 334 patients, 47 614 of whom were exposed to baclofen. Patients exposed to baclofen differed from those treated with approved drugs in terms of sociodemographic and medical characteristics (more females, higher socioeconomic status, fewer hospitalisations for alcohol-related problems), but these differences tended to fade at higher doses of baclofen. Baclofen exposure was significantly associated with hospitalisation (hazard ratio [HR] = 1.13 [95%CI: 1.09-1.17]) and death (HR = 1.31 [95%CI: 1.08-1.60]). The risk increased with dose, reaching 1.46 [1.28-1.65] for hospitalisation and 2.27 [1.27-4.07] for death at high doses. Similar results were in patients with a history of hospitalisation for alcohol-related problems. CONCLUSIONS: This study raises concerns about the safety of baclofen for AUD, particularly at high doses, with higher risks of hospitalisation and mortality than approved drugs.